Variant chr14-52011009-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007361.4(NID2):c.3589C>T(p.Arg1197Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

NID2
NM_007361.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

Variant links:

Genes affected

NID2 (HGNC:13389): (nidogen 2) This gene encodes a member of the nidogen family of basement membrane proteins. This protein is a cell-adhesion protein that binds collagens I and IV and laminin and may be involved in maintaining the structure of the basement membrane.[provided by RefSeq, Jun 2010]

NID2 links:

NID2 (HGNC:):

NID2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NID2	NM_007361.4 linkuse as main transcript	c.3589C>T	p.Arg1197Cys	missense_variant	18/22	ENST00000216286.10	NP_031387.3	Q14112-1
NID2	XM_005267405.5 linkuse as main transcript	c.3670C>T	p.Arg1224Cys	missense_variant	17/21		XP_005267462.1
NID2	XM_005267406.5 linkuse as main transcript	c.3526C>T	p.Arg1176Cys	missense_variant	16/20		XP_005267463.1
NID2	XM_005267407.5 linkuse as main transcript	c.3445C>T	p.Arg1149Cys	missense_variant	17/21		XP_005267464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NID2	ENST00000216286.10 linkuse as main transcript	c.3589C>T	p.Arg1197Cys	missense_variant	18/22	1	NM_007361.4	ENSP00000216286.4	Q14112-1
NID2	ENST00000556572.1 linkuse as main transcript	c.1393C>T	p.Arg465Cys	missense_variant	9/13	2		ENSP00000452190.1	H0YJV3
NID2	ENST00000553297.1 linkuse as main transcript	n.507C>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251440

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000766

AC:

112

AN:

1461860

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.0000917

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.3589C>T (p.R1197C) alteration is located in exon 18 (coding exon 18) of the NID2 gene. This alteration results from a C to T substitution at nucleotide position 3589, causing the arginine (R) at amino acid position 1197 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.044

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Benign

0.21

PROVEAN

Pathogenic

-4.4

D;.

REVEL

Benign

0.21

Sift

Uncertain

0.0030

D;.

Sift4G

Benign

0.070

T;T

Polyphen

1.0

D;.

Vest4

0.63

MutPred

0.59

Gain of catalytic residue at R1198 (P = 0);.;

MVP

0.58

MPC

0.49

ClinPred

0.70

GERP RS

5.1

Varity_R

0.38

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over